1. Field of the Invention
This invention relates to a novel process for the synthesis of certain allenic prostanoic acid derivatives, such derivatives being useful as intermediates in the preparation of synthetic prostaglandins which have the utility, for example, of gastric antisecretory activity.
2. Related Disclosures
Various methods for the preparation of allenes and allenic prostanoic acid derivatives are exemplified in the patent and chemical literature. See, for example, U.S. Pat. Nos. 3,879,438; 3,985,791; 4,418,206; 4,578,505; Tetrahedron Letters, 1975, pp 4615-4618, J.A.C.S., 1984, Vol. 106, 3368-3370. These references are variously concerned with the preparation of allenes via rearrangement of a propargylic ester with the requisite number of carbon atoms already in place by reaction with a lithium diorganocuprate. A method more closely related to the present invention is disclosed in U.S. Pat. No. 4,600,785, which describes the preparation of one embodiment of the intermediate of formula (2) in a racemic or optically pure form, and its subsequent two-carbon homologation accompanied by allene formation, by reaction with a trialkylorthoacetate (Claisen Rearrangement). However, to get to the desired corresponding embodiment of the compound of formula (I) it is then necessary to insert one more carbon atom between the allene moiety and the carboxyl group, a procedure involving four more steps.
The process described herein provides a more efficient method for the preparation of allenic prostanoic acid derivatives by three-carbon homologation of an intermediate of formula (2) with concomitant allene formation.
The disclosures of these, and all other documents referred to throughout the specification, are herein incorporated by reference.